Two issues will be pursued; the first relates to the interaction between alpha and beta (non alpha) globin chain synthesis, while the second involves characterization of the globin chains of normal rats as well as those synthesized by erythroleukemia cells in culture: (1) We have shown that specific inhibition of a chain synthesis leads to increased synthesis of beta chains by rabbit reticulocytes. This observation indicates that alpha chains do not assist in the synthesis of beta chains and suggests that alpha and beta mRNA compete for limiting component(s) of the translational apparatus. Using erythroid marrow from rabbits in short term culture, others have obtained results suggesting that in these nucleated cells with little or no pool of free alpha chains, alpha chain synthesis may be necessary for continued beta chain synthesis. We propose to re-examine this situation, using techniques that should control better for purity and prevention of proteolysis of beta chains. Avoiding excessive dilution of cells with media is critical in order to obtain the stimulation of beta chain synthesis that accompanied inhibition of alpha incorporation. We propose to determine the nature of the agent which appears to diffuse in and out of reticulocytes yet is clearly necessary for increased beta chain formation. (2) Adult rats have a multitude of hemoglobins representing at least 3 distinct alpha chains and 4 beta chains. We propose to complete efforts to determine the primary structure of these to find out how many nonallelic loci are expressed. In addition, others have shown that some of these chains are synthesized after dimethyl sulfoxide treatment of erythroleukemic rat cells. Information on the amino acid sequences will be valuable in elucidating how many globin loci respond to this developmental program.